PROJECT SUMMARY Candidate (Eric J. Gonzalez, PhD): My long-term career goal is to develop a peripheral nerve stimulation device to manage lower urinary tract symptoms and improve bladder emptying in underactive bladder. I am seeking a Mentored Research Scientist Development Award (K01) to expand my translational research program and develop leadership skills to independently manage a research team. The K01 award will provide me with mentored training in human subjects research, didactic clinical coursework, and protected time for professional development. Environment: My career development will be guided by a multidisciplinary team with proven expertise in neural engineering, clinical research, basic science, and biostatistics. My training will be implemented at Duke University, a world-class academic medical center with innovative scientific research laboratories and neighboring medical facilities that enable rapid translation of novel ideas. Research: Underactive bladder is an understudied health concern that occurs in diverse patient populations and exhibits an age-related increase in prevalence. The palliative management options for persons with underactive bladder are associated with poor quality of life and patients often fail to completely resolve lower urinary tract symptoms. In order to improve therapeutic outcomes, there is a need to clarify the pathological mechanisms underlying underactive bladder. The objective of this proposal is to determine the role of motor and sensory nerve drive in the development of underactivity in a novel animal model, as well as in women with underactive bladder. We will first utilize a novel rat model of underactivity to determine the mechanisms of reduced motor drive and efficacy of pharmacological treatments and electrical neuromodulation in improving bladder emptying (Aim 1). We will also quantify the contributions of reduced sensory drive to the pathophysiology of lower urinary tract symptoms in neurologically-intact adult women with underactive bladder and determine the efficacy of electrical neuromodulation in resolving symptoms (Aim 2). These studies will increase our understanding of the muscular and neural alterations in the lower urinary tract that may accompany underactive bladder and will provide a foundation for clinicians to develop innovative therapeutics to improve patient outcomes.